The overall objective of this work is to understand the mechanism of action of the bacterial ribosome in terms of the chemical structures of its macromolecular components. Our approach is to focus on two central ribosomal functions. tRNA binding and peptidyl transferase, to determine which components of the ribosomal structure contribute directly to these functional sites. An important model to be tested is the possible direct participation of ribosomal RNA as well as ribosomal proteins in these functions. Portions of the RNA and proteins which contribute to such 'composite sites' should be in close enough proximity to be cross-linked by multifunctional reagents which we have designed. Successful application of this approach, in combination with in vitro functional and reconstitutional techniques, should lead to new information about the chemical nature of ribosomal functional sites and their three-dimensional structures.